{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:09:50Z","timestamp":1791047390868,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,11,2]],"date-time":"2011-11-02T00:00:00Z","timestamp":1320192000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:p>Hernan I, Gamundi MJ, Borr\u00e0s E, Maseras M, Garc\u00eda\u2010Sandoval B, Blanco\u2010Kelly F, Ayuso C, Carballo M. Novel p.M96T variant of NRL and shRNA\u2010based suppression and replacement of <jats:italic>NRL<\/jats:italic> mutants associated with autosomal dominant retinitis pigmentosa.<\/jats:p><jats:p>Mutations in the gene encoding the transcription factor neural retina leucine zipper (<jats:italic>NRL<\/jats:italic>) are known to cause autosomal dominant (adRP) or recessive (arRP) retinitis pigmentosa (RP). In an adRP Spanish family, we detected a novel sequence variation (c.287T&gt;C) in the <jats:italic>NRL<\/jats:italic> gene that results in the p.M96T protein change. A functional test of the ability of NRL, in conjunction with cone\u2010rod homeobox (CRX), to transactivate a human rhodopsin (<jats:italic>RHO<\/jats:italic>) promoter was used to evaluate the pathogenic mechanisms of NRL. We found upregulation of the RHO promoter by p.M96T protein similar to that shown by other missense <jats:italic>NRL<\/jats:italic> mutations that cause adRP. Affected RP patients of the family carry the nucleotide change, although two other family members that also carry the c.287T&gt;C variation remain asymptomatic. This result complicates the genetic counselling of the family.<\/jats:p><jats:p>The pathogenic mechanisms associated with adRP <jats:italic>NRL<\/jats:italic> mutations appear to be caused by a gain of function. To suppress the negative effect of an NRL mutant, the suppression and replacement strategy seems to be the most suitable therapeutic approach capable of overcoming the mutational heterogeneity associated with <jats:italic>NRL<\/jats:italic>\u2010linked adRP. Thus, we evaluated this methodology in the <jats:italic>NRL<\/jats:italic> gene for the first time.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2011.01796.x","type":"journal-article","created":{"date-parts":[[2011,10,7]],"date-time":"2011-10-07T21:56:41Z","timestamp":1318024601000},"page":"446-452","source":"Crossref","is-referenced-by-count":13,"title":["Novel p.M96T variant of NRL and shRNA\u2010based suppression and replacement of <i>NRL<\/i> mutants associated with autosomal dominant retinitis pigmentosa"],"prefix":"10.1111","volume":"82","author":[{"given":"I","family":"Hernan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MJ","family":"Gamundi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Borr\u00e0s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Maseras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Garc\u00eda\u2010Sandoval","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Blanco\u2010Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Ayuso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Carballo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,11,2]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1135"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.120.3.369"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.121.6.793"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1443"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0408183101"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105855200"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508214103"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.06.036"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh173"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003658200"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20488"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.1.191"},{"key":"e_1_2_7_14_2","first-page":"2863","article-title":"Ribozyme\u2010based therapeutic approaches for autosomal dominant retinitis pigmentosa","volume":"41","author":"O\u2019Neill B","year":"2000","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1515\/CCLM.2000.022"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/0-387-32442-9_33"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.visres.2006.11.026"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302512"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2005.03.028"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1086\/519025"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.visres.2007.08.014"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20287"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.2174\/156652306775515592"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300116"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1399-0004.2011.01796.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1399-0004.2011.01796.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T03:49:41Z","timestamp":1698724181000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1399-0004.2011.01796.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,11,2]]},"references-count":23,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2012,11]]}},"alternative-id":["10.1111\/j.1399-0004.2011.01796.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1399-0004.2011.01796.x","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,11,2]]}}}